NM_001082971.2(DDC):c.260C>T (p.Pro87Leu) AND Deficiency of aromatic-L-amino-acid decarboxylase

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Sep 25, 2024
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001250058.9

Allele description [Variation Report for NM_001082971.2(DDC):c.260C>T (p.Pro87Leu)]

NM_001082971.2(DDC):c.260C>T (p.Pro87Leu)

Genes:

DDC-AS1:DDC antisense RNA 1 [Gene - HGNC]
DDC:dopa decarboxylase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7p12.1

Genomic location:

Preferred name:

NM_001082971.2(DDC):c.260C>T (p.Pro87Leu)

HGVS:

NC_000007.14:g.50539970G>A
NG_008742.1:g.30487C>T
NM_000790.4:c.260C>T
NM_001082971.2:c.260C>TMANE SELECT
NM_001242886.2:c.202-1991C>T
NM_001242887.2:c.260C>T
NM_001242888.2:c.201+3915C>T
NM_001242889.2:c.260C>T
NM_001242890.2:c.260C>T
NP_000781.2:p.Pro87Leu
NP_001076440.2:p.Pro87Leu
NP_001229816.2:p.Pro87Leu
NP_001229818.2:p.Pro87Leu
NP_001229819.2:p.Pro87Leu
NC_000007.13:g.50607668G>A
NC_000007.13:g.50607668G>A
NM_000790.3:c.260C>T
NR_033845.1:n.318G>A

Protein change:

P87L

Links:

dbSNP: rs746244631

NCBI 1000 Genomes Browser:

rs746244631

Molecular consequence:

NM_001242886.2:c.202-1991C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001242888.2:c.201+3915C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_000790.4:c.260C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001082971.2:c.260C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001242887.2:c.260C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001242889.2:c.260C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001242890.2:c.260C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_033845.1:n.318G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Deficiency of aromatic-L-amino-acid decarboxylase
Synonyms:: AADC DEFICIENCY; DDC DEFICIENCY; DOPA DECARBOXYLASE DEFICIENCY; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0012084; MedGen: C1291564; Orphanet: 35708; OMIM: 608643

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001424210	Elsea Laboratory, Baylor College of Medicine	no assertion criteria provided	Likely pathogenic (Apr 1, 2020)	paternal	clinical testing
SCV002205156	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 25, 2024)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 25001633, 32369189, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001424210

Elsea Laboratory, Baylor College of Medicine

no assertion criteria provided

Likely pathogenic
(Apr 1, 2020)

paternal

clinical testing

SCV002205156

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 25, 2024)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	paternal	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Widening Phenotypic Spectrum of AADC Deficiency, a Disorder of Dopamine and Serotonin Synthesis.

Helman G, Pappa MB, Pearl PL.

JIMD Rep. 2014;17:23-7. doi: 10.1007/8904_2014_327. Epub 2014 Jul 8. Erratum in: JIMD Rep. 2014;17:97. doi: 10.1007/978-3-662-44578-5_344..

PubMed [citation]

PMID:: 25001633
PMCID:: PMC4241195

AADC deficiency from infancy to adulthood: Symptoms and developmental outcome in an international cohort of 63 patients.

Pearson TS, Gilbert L, Opladen T, Garcia-Cazorla A, Mastrangelo M, Leuzzi V, Tay SKH, Sykut-Cegielska J, Pons R, Mercimek-Andrews S, Kato M, Lücke T, Oppebøen M, Kurian MA, Steel D, Manti F, Meeks KD, Jeltsch K, Flint L.

J Inherit Metab Dis. 2020 Sep;43(5):1121-1130. doi: 10.1002/jimd.12247. Epub 2020 May 14.

PubMed [citation]

PMID:: 32369189
PMCID:: PMC7540529

See all PubMed Citations (3)

Details of each submission

From Elsea Laboratory, Baylor College of Medicine, SCV001424210.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	paternal	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002205156.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 87 of the DDC protein (p.Pro87Leu). This variant is present in population databases (rs746244631, gnomAD 0.009%). This missense change has been observed in individual(s) with aromatic L-amino acid decarboxylase deficiency (PMID: 25001633, 32369189). ClinVar contains an entry for this variant (Variation ID: 973441). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt DDC protein function with a positive predictive value of 80%. For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Apr 28, 2025

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